Magnetic eye shields and methods of treatment and diagnosis using the same

ABSTRACT

In certain aspects, the invention is directed to magnetic eye shields that comprise a magnet. When worn by a patient, the magnetic eye shields are configured to generate an intraocular magnetic field of sufficient magnitude and direction to move a magnetic therapeutic and/or diagnostic agent positioned inside the eye to target tissue within the eye. Other aspects of the invention pertain to kits which comprise such magnetic eye shields as well as one or more additional components, for example, one or more containers of a magnetic diagnostic and/or or therapeutic agent. Further aspects of the invention pertain to methods of treatment, which comprise intraocularly introducing a magnetic therapeutic and/or diagnostic agent into an eye of a patient and fitting a magnetic eye shield to the head of the patient, wherein the magnetic therapeutic and/or diagnostic agent may be introduced to the patient before or after fitting the magnetic eye shield to the head of the patient.

STATEMENT OF RELATED APPLICATION

This application is a continuation application of U.S. Ser. No.14/706,701, filed May 7, 2015, which is a continuation-in-part ofinternational application Serial No. PCT/US2013/068397 filed Nov. 5,2013 and entitled “MAGNETIC EYE SHIELDS AND METHODS OF TREATMENT ANDDIAGNOSIS USING THE SAME,” which claims the benefit of U.S. Ser. No.61/723,475, filed Nov. 7, 2012 and entitled: “MAGNETIC EYE SHIELDS ANDMETHODS OF TREATMENT AND DIAGNOSIS USING THE SAME,” each of which ishereby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention is related to magnetic eye shields and to methodsof treatment and diagnosis using magnetic eye shields.

BACKGROUND

A large number of diseases and disorders result from the dysfunction ofa specific tissue or organ. A number of these diseases and disorders arecurrently treated by transplantation, e.g., heart transplantation forcertain types of cardiac dysfunction, corneal transplantation forcorneal endothelial cell dysfunction, stem cells for blood cancers, andso forth. However, transplantation procedures are invasive, have varyingrates of success, and are not available for many types of injuries,diseases or disorders, in particular for a number of eye diseases, forexample, including certain injuries or diseases of the cornea (e.g.,endothelial dystrophies, stromal dystrophies, bullous keratopathy,etc.), certain injuries or diseases of retinal ganglion cells and theoptic nerve (e.g., glaucoma, retinal artery or vein occlusions, ischemicoptic neuropathies, other optic neuropathies, etc.), and certaindiseases of retinal photoreceptors and retinal pigment epithelium (e.g.,Leber's congenital amaurosis, retinitis pigmentosa, age-related maculardegeneration, etc.) For ease of reference, various parts of the eye 10are shown in FIG. 1, specifically, the cornea 1, pupil 2, iris 3,ciliary muscle 6, lens 4, retina 5, optic nerve 7 and anterior chamber 8(which contains the aqueous humor), and vitreous cavity 9.

Although in many cases it would seem desirable to administer new“healthy” cells, for instance, by injection or infusion, simplyintroducing such cells into the eye generally does not work as they donot remain localized and adhere to or become incorporated into thetarget tissue of a patient. For example, healthy conical endothelialcells are inefficiently incorporated into a patient's diseased orinjured cornea when injected into the anterior chamber of the eye, withthe majority of cells simply falling by gravity away from the cornea,rather than properly attaching to the cornea (see, e.g., Mimura et al.,Invest. Ophthalmol. Vis. Sci. 2005, 46(10):3637-44). Similarly, healthyretinal ganglion cells are not incorporated into the retina wheninjected into the vitreous cavity of the eye (see, e.g., U.S.2011/0003003 to Goldberg et al., the disclosure of which is herebyincorporated by reference).

SUMMARY OF THE INVENTION

In certain aspects, the invention is directed to magnetic eye shieldsthat comprise a magnet. When worn by a patient, the magnetic eye shieldsare configured to generate an intraocular magnetic field of sufficientmagnitude and direction to move a magnetic therapeutic and/or diagnosticagent positioned inside the eye to a target tissue within the eye. Insome embodiments, the magnetic eye shield is selected from eye patches,or eyeglasses and goggles, among other possibilities.

Other aspects of the invention pertain to kits which comprise suchmagnetic eye shields as well as one or more additional components, forexample, one or more containers of a magnetic diagnostic and/or ortherapeutic agent.

Further aspects of the invention pertain to methods of treatment, whichcomprise intraocularly introducing a magnetic therapeutic and/ordiagnostic agent into an eye of a patient and fitting a magnetic eyeshield to the head of the patient. The magnetic eye shield is configuredto generate an intraocular magnetic field of sufficient magnitude anddirection to move the magnetic therapeutic and/or diagnostic agentpositioned inside the eye to a target tissue within the eye, and themagnetic therapeutic and/or diagnostic agent may be introduced to thepatient before or after fitting the magnetic eye shield to the head ofthe patient.

These and various other aspects and embodiments and as well asadvantages of the present invention will become immediately apparent tothose of ordinary skill in the art upon review of the DetailedDescription and any appended claims to follow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a human eye in accordance with theprior art.

FIG. 2A is a schematic illustration of a bar magnet and associated fieldlines, in accordance with the prior art.

FIG. 2B is a schematic illustration of a ring-shaped magnet andassociated field lines, in accordance with the prior art.

FIG. 3 is a schematic illustration of an eye shield with an associatedring-shaped magnet like that of FIG. 2B, in accordance with anembodiment of the present invention.

FIG. 4 is a schematic illustration showing an eye shield like that ofFIG. 3 in close proximity to the eye, in accordance with an embodimentof the present invention.

FIG. 5 is a schematic illustration of a pair of eyeglasses with anassociated electromagnet, in accordance with an embodiment of thepresent invention.

FIG. 6 is a schematic illustration of an eye patch with an associatedelectromagnet, in accordance with an embodiment of the presentinvention.

FIG. 7 is a schematic illustration of an eye patch with an associatedring- shaped magnet like that of FIG. 2B, in accordance with anotherembodiment of the present invention.

FIG. 8 is a schematic illustration of a cross-section of a bar magnetand associated field lines, for use in various embodiments of theinvention.

FIG. 9 is a schematic illustration of a cylindrical magnet for use inaccordance with an embodiment of the present invention.

FIG. 10A and 10B are schematic illustrations of eye cups for use asalignment components, in accordance with two embodiments of the presentdisclosure.

FIG. 11 is a graph of measured magnetic field emanating from a magnetthat is shielded by 1, 2 and 4 sheets of shielding material, as afunction of distance from the shielding material, in accordance with anembodiment of the present disclosure.

FIG. 12 is a graph of measured magnetic field emanating from a magnetthat is shielded by 1, 2, 4 and 6 sheets of shielding material, as afunction of distance from the shielding material, in accordance with anembodiment of the present disclosure.

DETAILED DESCRIPTION OF THE INVENTION

A more complete understanding of the present invention is available byreference to the following detailed description of numerous aspects andembodiments of the invention. The detailed description of the inventionwhich follows is intended to illustrate but not limit the invention.

In the present disclosure, external magnetic eye shields are providedwhich are adapted to preferentially position magnetic diagnostic and/oror therapeutic agents which are placed within the eye of a subject for avariety of purposes. Though there are many eye shields for novelty,corrective or protective purposes, no shield is known to be availablethat by design provides a specifically desired intraocular magneticfield.

As used herein, “subjects” (also referred to as “patients”) arevertebrate subjects, more typically mammalian subjects, including humansubjects, pets and livestock.

Most materials can be classified as diamagnetic, paramagnetic,ferromagnetic or ferrimagnetic. Diamagnetic materials have a weak,negative susceptibility to magnetic fields and are thus slightlyrepelled by a magnetic field. Most elements in the periodic table,including copper, silver, and gold, are diamagnetic. Paramagneticmaterials have a small, positive susceptibility to magnetic fields andare thus slightly attracted by a magnetic field. Paramagnetic materialsinclude magnesium, molybdenum, lithium, and tantalum. Ferromagnetic andferrimagnetic materials have a large, positive susceptibility to anexternal magnetic field and thus are strongly attracted by a magneticfield. Examples of ferromagnetic materials include iron, nickel, cobaltand some rare earth elements (e.g., gadolinium, dysprosium, etc.).Examples of ferrimagnetic materials include magnetite, maghemite andvarious ferrites including nickel ferrite, cobalt ferrite, manganeseferrite, nickel zinc ferrite and manganese zinc ferrite.Superparamagnetism is a form of magnetism, which appears in smallferromagnetic or ferrimagnetic nanoparticles (e.g., small particlesranging from 1-25 nm in diameter, more typically, 1-10 nm in diameter).Superparamagnetic materials are attracted by a magnetic field but relaxtheir magnetic dipole when the field is removed, decreasing theirability to attract each other in the absence of an external magneticfield. For diagnostic and therapeutic use, this relaxation may providecertain advantages, in some embodiments.

In the present disclosure, magnetic diagnostic and/or or therapeuticagents are preferably ferromagnetic or ferrimagnetic in nature, and morepreferably superparamagnetic in certain applications. Specific examplesof therapeutic agents include magnetic cells, for examples magnetic stemcells or magnetic ocular cells such as magnetic corneal endothelialcells and magnetic retinal pigment epithelial cells or magneticphotoreceptor cells. Further specific examples of magnetic therapeuticagents include magnetic growth factors, small molecule drugs, biologicaltherapeutics, antibodies or antibody fragments, or cytokines. Specificexamples of diagnostic agents include diagnostic agents such as magneticfluorescent dyes, magnetic antibodies or antibody fragments, or magneticparticles that could be paired with diagnostic imaging or sensingdevices such as optical coherence tomography, ultrasound, andphotographic filters. Various materials can be rendered ferromagnetic orferrimagnetic by associating them with ferromagnetic or ferrimagneticparticles such as microparticles or nanoparticles. For instance, (a) theagents can be attached to the surface of the particles by covalentinteractions and/or non-covalent interactions (e.g., interactions suchas van der Waals forces, hydrophobic interactions and/or electrostaticinteractions, for instance, charge-charge interactions, charge-dipoleinteractions, and dipole-dipole interactions, including hydrogenbonding), (b) the agents can be applied as a coating (biostable orbiodegradable) that at least partially surrounds the particles, or (c)the particles can be bound to or endocytosed by the agent (e.g., a cell)and in either or both cases incorporated into the inside of the agent.

The eye shields of the present disclosure may cover one eye or botheyes. Moreover, the eye shields may be transparent (i.e., having atransmission of visible light of at least 20%), opaque or a combinationof both. For example, in certain embodiments, the eye shield may be inthe form of an eye patch that covers one or both eyes. In certainembodiments, the eye shield of the present disclosure may betransparent, in which case the eye shield may or may not provide visioncorrection for one or both eyes (e.g., an eye shield in the form ofsafety glasses, eyeglasses, safety goggles, corrective goggles,monocles, etc.). In certain embodiments the eye shield is positioned ata distance from the eye ranging from 5 to 20 mm (e.g., for eyeglasses orother shield where the patient opens his/her eyes). In certainembodiments the eye shield may sit flush with the eyelid in a closedposition. In certain embodiments the eye shield may be concave to theeye and rest against the orbital rim peripherally. In certainembodiments the eye shield may rest directly on the cornea.

In order to generate a magnetic field having a desired magnitude anddirection, the magnetic eye shields of the present disclosure areprovided with one or more suitable magnets which may be selected, forexample, from temporary magnets, permanent magnets and electromagnets.

Examples of permanent and temporary magnets include magnets thatcomprise iron, magnets that comprise neodymium, magnets that comprisecobalt, and magnets that comprise boron. Specific examples include rareearth magnets such as magnets that comprise neodymium, iron and boron(e.g., neodymium-iron-boron magnets, which commonly contain an alloy ofneodymium, iron and boron, commonly in the form of a Nd₂Fe₁₄B tetragonalcrystalline structure), magnets that comprise samarium and cobalt (e.g.,samarium-cobalt magnets, which are commonly available in two “series”,specifically Series 1:5, which contain one atom of rare earth samariumfor every five atoms of cobalt, and Series 2:17, which contain two atomsof rare-earth samarium and 13-17 atoms of transition metals, with thetransition metal content being rich in cobalt). Specific examplesfurther include magnets that comprise iron (e.g., ferrite magnets, whichcommonly have iron(III) oxide as the principle component) and magnetsthat comprise iron, aluminum, nickel and cobalt (e.g., Alnico magnets,which typically contain 8-12% Al, 15-26% Ni, 5-24% Co, up to 6% Cu, upto 1% Ti, and the balance Fe).

Specific examples of magnets include neodymium magnets. Neodymiummagnets have a simple nomenclature, with the various grades starting “N(industry simplification of Neodymium) and is followed by a two digitnumber. This number represents the maximum energy product in Mega-GaussOersteds (MGOe). Neodymium magnets are commercially available in gradesranging from grade N24 up to grade N52, with a potential maximum ofgrade N64. In certain beneficial embodiments, neodymium magnets areemployed with strength grade ranging from grade N42 to grade N64, morebeneficially, ranging from grade N52 to grade N64.

An electromagnet is a type of magnet in which a magnetic field isproduced by the flow of electric current, with the strength of magneticfield generated being proportional to the amount of current. Themagnetic field disappears when the current is turned off. Typically,electromagnets comprise a conductor (e.g., an insulated wire, a printedor etched conductive line, etc.) in the form of a coil. To increase themagnetic field, a coil with multiple turns may be employed. The magneticfield may be increased by positioning a ferromagnetic material (e.g.,iron, etc.) inside the coil to produce a ferromagnetic-coreelectromagnet.

Where an electromagnet is employed in the eye shields of the presentdisclosure, a power source is also typically provided. The power sourcemay include, for instance, a non-rechargeable battery or may include arechargeable battery, which may be recharged, for instance, byconnection to an external voltage source via a conductor (e.g., via awire connection) or by wireless recharging (e.g., by inductivecharging). The power source may also include components which controlthe current within the electromagnet (and thus the field strength of theelectromagnet) and which control the duty cycle of the electromagnet, inother words that amount of time and frequency the electromagnet is “on”(and generating a magnetic field) and when it is “off” (and notgenerating a field). One advantage of the use of an electromagnet inthis embodiment is the ability to titrate the field strength exerted bythe magnetic eye shield invention by changing the input current to theelectromagnet.

For purposes of illustration, two magnets and their associated magneticfield lines are shown schematically in FIGS. 2A and 2B.

FIG. 2A is a schematic illustration of a simple bar magnet 110 (e.g., arare earth magnet, ferrite magnet, Alnico magnet, etc.) and the magneticfield lines associated with that magnet.

FIG. 2B is a schematic illustration of a ring-shaped magnet 110 and themagnetic field lines associated with the magnet. The ring-shaped magnet110 may be for example, a temporary or permanent magnet (e.g., a rareearth, ferrite or Alnico magnet with poles on opposing faces of thering) or the ring-shaped magnet 110 may be an electromagnet.

“Magnetic field lines” are lines that are drawn to show the direction ofa magnetic field created by a magnet. These lines are also called “linesof force”. Magnetic materials that are sufficiently mobile will migrateas a result of a magnetic field.

In various aspects, the present disclosure is directed to eye shieldsthat generate an intraocular magnetic field that is sufficient tophysically direct a magnetic therapeutic and/or diagnostic agent (e.g.,a ferromagnetic material, ferrimagnetic material, etc.) positionedinside of the eye (e.g., placed in the eye by a patient or health careprovider via surface application, infusion, injection, implantation,etc.) to one or more target tissues within the eye.

For instance, in one particular embodiment, the eye shield may generatea magnetic field having a magnitude and direction such that a magneticdiagnostic and/or therapeutic agent positioned in the anterior chamberof the eye is directed to the back surface of the cornea.

In another particular embodiment, the eye shield may generate a magneticfield having a magnitude and direction such that a magnetic diagnosticand/or therapeutic agent positioned in the vitreous cavity of the eye isdirected towards the posterior pole of the eye.

FIG. 3 is a schematic illustration of an eye shield 210 in accordancewith the present disclosure within which is disposed a ring-shapedmagnet 110 like that of FIG. 2B. The eye shield may be associated, forexample, with an eye patch, eyeglasses, goggles or a variety of otherdevices. As seen schematically in FIG. 4, when an eye shield 210 withmagnet 110 like that of FIG. 3 is placed adjacent to an eye 10, themagnetic field lines associated with such a device penetrate the eye,thereby exerting a force on any magnetic material that is disposedwithin the eye; that force may be attractive or repulsive.

While a ring-shaped magnet like that of FIG. 2B is shown in FIGS. 3 and4, it should be clear from the present disclosure that the invention isnot limited to such a magnet. Other types of magnets may be employed solong as a magnetic field is established within the eye that is capableof directing a magnetic therapeutic and/or diagnostic agent positionedwithin the eye to a targeted position within the eye.

Different magnetic fields can be used to attract or repel magneticagents to different locations within the eye. In some embodiments, amagnet placed anterior to the eye will apply an attractive force to amagnetic material (e.g., a paramagnetic, ferromagnetic or ferrimagneticmaterial) within the eye in a direction that includes an anterior vectorcomponent. Consequently, magnets incorporated into external eye shieldsin accordance with the present disclosure may be used to drawintraocular magnetized material to the anterior aspect of the eye fordiagnostic or therapeutic purposes. In other embodiments, a magnetplaced anterior to the eye will apply a repulsive force to a magneticmaterial (e.g., a diamagnetic material) within the eye in a directionthat includes a posterior vector component. Thus, a diamagnetic materialmay be used which is repulsed from the magnetic field, and, as in theabove description, may drive the therapeutic and/or diagnostic agent tothe posterior aspect of the eye.

The one or more magnets provided within the eye shields typicallygenerate a magnetic field strength, measured at a distance from themagnet equal to the distance of the magnetic eye shield from the eye inthat particular embodiment, ranging from 0.01 Tesla or less to 5 Teslaor more (e.g., ranging from 0.01 Tesla to 0.025 Tesla to 0.05 Tesla to0.1 Tesla to 0.25 Tesla to 0.5 Tesla to 1.0 Tesla to 2.5 Tesla to 5.0Tesla). More typical magnetic field strengths may range from 0.1 to 1.0Tesla in order to allow a force sufficient to cover the 24 mm axiallength of a typical human eye. The actual field strength will varydepending on various factors including the distance between the eyeshield and the eye (e.g., the corneal apex), the depth of the targettissue within the eye, and the responsiveness or magnetic susceptibilityof the therapeutic and/or diagnostic agent to the magnetic field, amongother factors.

In some embodiments, the eye shields of the present disclosure areconfigured to provide a magnetic field of constant field strength intime. In other embodiments, the eye shields of the present disclosureare configured to provide a magnetic field of variable field strength asfunction of time. For example, it may be advantageous to be able tocreate a magnetic field that has an on/off duty cycle to control theextent and duration of the magnetic field, or to reverse the polarity.This may be able to help a magnetic agent placed inside the eye tocirculate for extended periods of time within the eye. In anotherexample, it may be advantageous to vibrate the magnetic agent inside theeye to generate mechanical forces or heat. In another example, it may beadvantageous to titrate a magnetic field strength up or down to maximizethe proposed delivery of the magnetic diagnostic and/or therapeuticdevice adjacent to or inside the eye.

Turning now to FIG. 5, a magnetic eye shield 210 in accordance with anembodiment of the present disclosure is schematically shown. Themagnetic eye shield 210 shown includes a frame 510 with two lenses 520,which may be corrective or non-corrective. The magnetic eye shield 210also includes two electromagnets 110 each of which comprises aconductive coil having one or more loops, which may be formed usinglines of a transparent conductor (e.g., formed of indium tin oxide,fluorine doped tin oxide, doped zinc oxide, etc.) or using an opaqueconductor (e.g., a metallic conductor such as copper, silver, gold,aluminum, etc.). In some embodiments, the center of each coil iscentered on the optical axis of each eye. The magnetic eye shield 210further includes two power supplies 310 which are connected to theelectromagnets 110 via conductive lines 320 which, like the coils of theelectromagnet 110, may be formed using a transparent conductor or anopaque conductor. The frame 510 may be secured to the head of thesubject, for example, by traditional eyeglass temples (not shown).

Numerous variations are of course possible including one or more of thefollowing among others: a single power supply may be used rather than apair of supplies, the power supply/supplies may be located in thesecurement structure (e.g., temple) of the device, a temporary orpermanent magnet may be used instead of an electromagnet (in which casethere would be no need for the power supplies and conductive lines), theeyeglass frame may be replaced with a goggle frame, a strap may be used(rather than temples) as a securement structure, and the magnet may belocated only on one side, i.e., the magnetic field may be applied toonly one eye.

A magnetic eye shield 210 in accordance with another embodiment of thepresent disclosure is schematically shown in FIG. 6. The magnetic eyeshield 210 shown includes an eye patch 610 which may include asecurement structure such as an adhesive strip 620. The magnetic eyeshield 210 also includes an electromagnet 110 which comprises aconductive coil having one or more loops, which may be formed using asuitable conductor, for instance, a transparent or opaque conductor suchas those listed above, among others. In some embodiments, the center ofeach coil is centered on the optical axis of the eye. In some otherembodiments, the center of the resultant magnetic field will beadjustable by being able to move (e.g., slide) the coil relative to theeye shield and thus permit treatment of the center of the optical axisfor patients with strabismus (paralytic or restrictive) and thus anoff-center optical axis. The magnetic eye shield 210 further includes apower supply 310 which is connected to the electromagnet 110 viaconductive lines 320 formed of a suitable conductor.

As in FIG. 5, numerous variations are possible for the eye shield ofFIG. 6 including one or more of the following among others: othermethods of securement may be used including a strap, which may beelastic (the strap can extend around the head in order to secure it overthe eye and be adjusted to ensure patient comfort), powersupply/supplies may be located in the securement structure (e.g., strap)of the device, a temporary or permanent magnet may be used instead of anelectromagnet (in which case there would be no need for the power supplyand conductive lines), the shield may configured to sit flush with theeyelid or it may be concave to the eye and thus rest against the orbitalrim peripherally.

One advantage of a patch (which contacts the eye or the eyelid) relativeto glasses/goggles (which do not) is that a magnet with a lower powermagnetic field may be employed to achieve a given intraocular fieldstrength due to the differing distances from the eye.

As previously indicated, in certain preferred embodiments, eye shieldsof the present disclosure are provided with magnetic fields that arecentered with the optical axis of the eye (see, e.g., the schematicillustration in FIG. 4) so as to direct magnetic therapeutic and/ordiagnostic agents which have been positioned within the eye toward theoptical axis of the eye. Because the magnet is disposed anterior to theeye, the magnetic field for such devices will be the strongest at theapex of the cornea. Consequently, magnetic therapeutic and/or diagnosticagents placed in the anterior chamber of the eye can be directed to thecenter of the cornea along the endothelial surface. In certainembodiments, this will help prevent the magnetic therapeutic and/ordiagnostic agents from settling into the inferior anterior chamber wherethe cells may clog the trabecular meshwork and limit aqueous egress fromthe eye. Additionally, this will direct the material into the opticalaxis where a therapeutic and/or diagnostic effect is desired.

In certain embodiments a magnet having a cylindrical shape is positioneddirectly over the corneal apex. Such a magnet 90 is shown in FIG. 9A.Cylindrical magnets are beneficial in that the magnetic field of magnetsof this type is typically strongest at the center of each of theopposing circular plates 90 p (one plate associated with the north poleof the magnet and the other plate associated with the south pole of themagnet), with the magnetic field decreasing as one proceeds radiallyfrom the center of the plates 90 p and as one proceeds normally from thesurface of the plates 90 p. Moreover, the smooth plates of cylindricalmagnets add to patient comfort, as there are no sharp corners or edgeson the magnet faces, which can rest directly on the patient's eyelid, ifdesired. In certain beneficial embodiments the magnet may be a neodymiummagnet of grade 50N or more. In certain beneficial embodiments themagnet may have a diameter ranging from 6 mm to 20 mm in diameter, moretypically ranging from 8 mm to 16 mm in diameter, and ranging from 5 mmto 40 mm in length, more typically ranging from 10 mm to 25 mm inlength. Either the north pole of the magnet or the south pole of themagnet may face the patient's eye.

In other embodiments, magnetic eye shields may be configured to generatean intraocular magnetic field that is strongest in a position other thanthe corneal apex. For example, the magnetic eye shield may be configuredto generate an intraocular magnetic field that is strongest at theperiphery of the cornea, for example, at the iridocorneal angle (wherethe base of the iris attaches to the peripheral cornea and sclera),among other locations. These embodiments may be useful, for example, intreatment of glaucoma using trabecular meshwork cells, among othertreatments.

In some embodiments, a magnet having a magnetic field like that of FIG.2B may be used to form a magnetic eye shield in which the magnet and itsassociated magnetic field are off-center with respect to the center ofthe eye shield. One example of an eye shield 210 with such an off-centermagnet 110 is shown schematically in FIG. 7.

In other embodiments, a magnet may be employed which is on-center withthe regard to the eye shield and which nevertheless does not generate anintraocular magnetic field that is strongest at the corneal apex. Forexample, a ring-shaped magnet 110 like that shown in schematiccross-section in FIG. 8 (where D is the inside diameter of the magnet)may be employed, in which one surface represents a north pole of themagnet and another opposing surface represents a south pole of themagnet. Such a magnet is capable of providing a circular region ofmaximum intraocular field strength whose diameter can be adjusted basedon the diameter of the magnet. For example, the diameter of the magnetmay be adjusted to provide a maximum intraocular field strength at theperiphery of the cornea, as indicated above. In this instance, thecenter of the magnet is preferably centered with respect to the eyeshield. In other embodiments, the center of such a magnet may beoff-center with regard to the eye shield.

In some embodiments, eye shields in accordance with the presentdisclosure are provided with a magnetic shielding material, in order toreduce or eliminate interactions between the one or more magnetsassociated with the eye shield and objects (e.g., ferromagnetic orferromagnetic objects) in the environment surrounding the patientincluding, for example, metal door frames and various loose metallicobjects that may be nearby. Examples of magnetic shielding materialsinclude various high-permeability shielding alloys such as nickel-ironalloys including permalloy (an alloy of nickel and iron) and mu-metal(an alloy of nickel, iron, copper and molybdenum or chromium),cobalt-based alloys, and ultra-low carbon steel, among others.

Where the eye shield is an eye patch, in order to enhance patient fitand comfort, it may be desirable to select a flexible or semi-rigidshielding material, for example, one or more sheets of flexible orsemi-rigid material made of alloy that is used to reduce or eliminate anexternal magnetic field. Such materials are beneficially materials ofhigh permeability and/or high saturation. Specific examples of suchmaterials include MagnetShield™, which has a reported initialpermeability of 200 and a saturation induction of 2.14 Tesla, andGiron™, which has a reported initial permeability of 500 and asaturation induction of 2 Tesla. Beneficially, the magnetic shieldingmaterial will be less than 3 mm in thickness, more beneficially lessthan 2 mm

Where the eye shield is an eye patch, it may be desirable to provide theeye shield with an alignment component that is concave to the eye,thereby improving the ease at which the magnet is aligned relative tothe eye (e.g., centered relative to the optical axis of the eye,positioned peripherally relative to the optical axis of the eye, etc.).For instance, in certain embodiments, the patch may incorporate as analignment component an eye cup analogous to those used in tanning bedgoggles (e.g., eye cup 95 in FIG. 10A) or a more spherical eye cup(e.g., eye cup 95 in FIG. 10B) which have a concave portion havingdimensions that are somewhat complementary to the patient's eyeball andeyelid. Hole 95 h may be aligned up with the optical axis of thepatient's eye or offset relative to the optical axis of the eye. Hole 95h may be configured to receive and hold in place a magnet (e.g., acylindrical magnet, among other possible shapes).

Further aspects of the present disclosure pertain to methods oftreatment of a subject.

In a typical procedure, a magnetic therapeutic and/or diagnostic agentis introduced into the eye, for example, by injection, implantation,infusion, or surface application, among other techniques. Injection orimplantation may be preferred in certain embodiments as more control isprovided other than placement of the material within the eye which, inturn, assists in directing the agent to target tissue of choice. Amagnetic eye shield such as one of those described elsewhere herein isalso fitted to the head of the subject, either prior or subsequent tothe introduction of the magnetic therapeutic and/or diagnostic agent. Invarious embodiments, care is taken to ensure that the magnetic field ofthe device is centered on the optical axis of the eye, as previouslynoted.

The eye shield is left in position for a time that is dependent uponvarious factors including the type of magnetic therapeutic and/ordiagnostic agent employed and the length of time required to see aclinical effect, whether for therapeutic or diagnostic purposes. Thetime frame may varying anywhere from 10 minutes to indefinitely. Typicaltime frames may range, for example, from 3 hours to 72 hours, amongothers.

The eye shield may or may not be coated or covered or surrounded by amaterial that provides appropriate comfort or biocompatibility duringits application. Such material could include but not be limited to anycombination of polymers such as silicones, silicone hydrogels or otherhydrogel materials (e.g., materials containing homopolymers orcopolymers of two or more hydrogel monomers, such as 2-hydroxyethylmethacrylate, 1-vinyl-2-pyrrolidone, methacrylic acid, etc.), cottonmaterials, or other suitable materials.

In one particular embodiment, a procedure is provided in which amagnetic therapeutic and/or diagnostic agent is introduced into theanterior chamber, and a magnetic shield may be worn to draw thosematerials anteriorly to the apical aspect of the corneal endothelium.For example, magnetic corneal endothelial cells can be injected in tothe anterior chamber of one or both eyes and a magnetic patch can beworn for anywhere from 10 minutes to indefinitely but typically for 1-3days after injection to stimulate migration of the injected conicalendothelial cells to the back surface of the cornea to facilitateintegration and retention of these cells into the host conicalendothelium.

Still further aspects of the present disclosure pertain to kits that areuseful for diagnosing or treating a patient. The kits may include all ora subset of all the components useful for treating or diagnosing apatient in accordance with the present disclosure. The kits may include,for example, any combination of two or more of the following items: (a)a magnetic eye shield in accordance with the present disclosure (e.g.,one or more eye patches, glasses, goggles, etc.), (b) a securementmaterial such a strap or a suture material or an adhesive compositionfor affixing the eye shield to a patient's head, (c) one or morecontainers of a magnetic diagnostic and/or or therapeutic agent, forexample, in a form that is suitable for immediate administration to apatient (e.g., in a liquid form suitable for injection, infusion orsurface application, in a dry form suitable for implantation, etc.) orin a form suitable for administration upon addition of another component(e.g., in a dry form that is suitable for administration upon suspensionor dissolution using a suitable liquid carrier, (d) one or morecontainers of a suitable liquid carrier (e.g. sterile water forinjection, physiological saline, phosphate buffer, phosphate bufferedsaline, etc.) which may be used to reconstitute a magnetic diagnosticand/or or therapeutic agent in dry form or may be used to dilute amagnetic diagnostic and/or or therapeutic agent in liquid form, (e) aninjection device (e.g., a combination syringe and needle or aniontophoresis device for administering a composition comprising amagnetic diagnostic and/or or therapeutic agent to the patients eye),(f) instructions for administering the magnetic compositions to apatient's eye and/or for fitting the magnetic eye shield to a patient'shead, (g) packaging and information as required by a governmentalregulatory agency that regulates cell therapy products, pharmaceuticalsand/or medical devices, and (h) appropriate anesthetic and antisepticsupplies. In certain embodiments, the components of the kits areprovided in a single sterile package for convenient use by a health careprofessional.

Where the kit comprises a magnet that is not an electromagnet (e.g., arare earth magnet, ferrite magnet, Alnico magnet, etc.) in combinationwith a ferromagnetic or ferromagnetic diagnostic and/or therapeuticagent, it may be desirable to provide the kit with shielding tomagnetically isolate the ferromagnetic or ferromagnetic agent from themagnet. For instance, if exposed to a magnetic field of sufficientmagnitude for a sufficient time, the ferromagnetic or ferromagneticdiagnostic and/or therapeutic agent may itself become magnetized, whichmay lead, for example to clumping of the agent. In embodiments whereshielding is desired, the ferromagnetic or ferromagnetic diagnosticand/or therapeutic agent, the magnet, or both may be enclosed within asuitable magnetic shielding material. Examples of magnetic shieldingmaterials include various high-permeability shielding alloys such asnickel-iron alloys including permalloy (an alloy of nickel and iron) andmu-metal (an alloy of nickel, iron, copper and molybdenum or chromium),cobalt-based alloys, and ultra-low carbon steel, among others.Additional aspects of the invention are set forth in the followingenumerated paragraphs:

Aspect 1. A magnetic eye shield comprising a magnet that when worn by apatient is configured to generate an intraocular magnetic field ofsufficient magnitude and direction to move a magnetic therapeutic and/ordiagnostic agent positioned inside the eye to a target tissue within theeye.

Aspect 2. The magnetic eye shield of aspect 1, wherein the magnetic eyeshield is selected from an eye patches, eyeglasses and goggles.

Aspect 3. The magnetic eye shield of any of aspects 1-2, wherein themagnetic field generated by the magnet ranges from 0.1 Tesla to 10.0Tesla.

Aspect 4. The magnetic eye shield of any of aspects 1-3, wherein themagnet is a rare earth magnet.

Aspect 5. The magnetic eye shield of any of aspects 1-3, wherein themagnet is an electromagnet comprising a conductive coil and a source ofelectrical power in electrical communication with the conductive coil.

Aspect 6. The magnetic eye shield of any of aspects 1-5, wherein themagnetic eye shield is configured to center the magnetic field of themagnet with the optical axis of the eye.

Aspect 7. The magnetic eye shield of any of aspects 1-5, wherein themagnetic eye shield is configured to generate an intraocular magneticfield that is strongest at the periphery of the cornea.

Aspect 8. The magnetic eye shield of any of aspects 1-5, wherein themagnetic eye shield is configured to generate an intraocular magneticfield that is strongest at the apex of the cornea.

Aspect 9. The magnetic eye shield of any of aspects 1-8, wherein themagnetic eye shield comprises a plurality of magnets.

Aspect 11. The magnetic eye shield of any of aspects 1-8, wherein themagnetic eye shield comprises a securement structure that is adapted tosecure the magnetic eye shield to the head of the patient.

Aspect 12. The magnetic eye shield of aspect 10, wherein the securementstructure is selected from a strap and adhesive strip.

Aspect 13. The magnetic eye shield of any of aspects 1-11, wherein themagnetic therapeutic and/or diagnostic agent is a ferromagnetic orferrimagnetic therapeutic and/or diagnostic agent.

Aspect 14. The magnetic eye shield of any of aspects 1-13, wherein themagnetic eye shield further comprises one or more sheets of magneticshielding material.

Aspect 15. The magnetic eye shield of any of aspects 1-13, wherein themagnetic eye shield further comprises two or more sheets of magneticshielding material.

Aspect 16. The magnetic eye shield of any of aspects 14-15, wherein themagnetic shielding material is less than 3 mm in thickness.

Aspect 17. The magnetic eye shield of any of aspects 1-16, wherein themagnetic eye shield further comprises an alignment component aligning apatient's eye with respect to the magnetic field.

Aspect 18. The magnetic eye shield of any of aspects 1-16, wherein themagnetic eye shield further comprises an eye cup configured to align apatient's eye with respect to the magnetic field.

Aspect 19. A kit comprising a magnetic eye shield in accordance with anyof aspects 1-18 and a container of a magnetic diagnostic and/or ortherapeutic agent.

Aspect 20. The kit of aspect 19, further comprising an injection device.

Aspect 21. The kit of any of aspects 19-20, wherein the magnetictherapeutic and/or diagnostic agent is a ferromagnetic or ferrimagnetictherapeutic and/or diagnostic agent.

Aspect 22. The kit of any of aspects 19-20, wherein the magnetictherapeutic and/or diagnostic agent is selected from one or more ofmagnetic stem cells, magnetic corneal endothelial cells, magneticretinal pigment epithelial cells, magnetic trabecular meshwork cells,magnetic antibodies, magnetic growth factors, and magnetic cytokines.

Aspect 23. The kit of any of aspects 19-22, wherein the magnet is anelectromagnet comprising a conductive coil and wherein the kit furthercomprises an inductive charging unit.

Aspect 24. A method of treatment comprising intraocularly introducing amagnetic therapeutic and/or diagnostic agent into an eye of a patientand fitting a magnetic eye shield to the head of the patient, whereinthe magnetic eye shield is configured to generate an intraocularmagnetic field of sufficient magnitude and direction to move themagnetic therapeutic and/or diagnostic agent positioned inside the eyeto a target tissue within the eye and wherein the magnetic therapeuticand/or diagnostic agent may be introduced to the patient before or afterfitting the magnetic eye shield to the head of the patient.

Aspect 25. The method of aspect 24, wherein the magnetic therapeuticand/or diagnostic agent is injected into the anterior chamber of the eyeand wherein the magnetic therapeutic and/or diagnostic agent is directedto the apex of the cornea.

Aspect 26. The method of aspect 24, wherein the magnetic therapeuticand/or diagnostic agent is injected into the anterior chamber of the eyeand wherein the magnetic therapeutic and/or diagnostic agent is directedto the periphery of the cornea.

Aspect 27. The method of any of aspects 24-26, wherein the magnetictherapeutic and/or diagnostic agent is selected from one or more ofmagnetic stem cells, magnetic corneal endothelial cells, magneticretinal pigment epithelial cells, magnetic trabecular meshwork cells,magnetic antibodies, magnetic growth factors, and magnetic cytokines.

Aspect 28. The method of any of aspects 24-27, wherein the magnetictherapeutic and/or diagnostic agent is selected from magnetic drugs andbiological therapeutics.

EXAMPLE

Construction of an eye patch in accordance with an embodiment of thepresent disclosure will now be described. The eye patch comprisesseveral components which will now be described.

The magnet in this Example is a neodymium magnet having a diameter ofabout 10 to 15 mm and a length of about 10 to 25 mm, for instance, azinc coated N52 neodymium magnet having a diameter of 12.75 mm and alength of 20 mm, available, for example, from K&J Magnetics, Inc.,Pipersville, Pa., USA.

The magnetic shielding component in this Example is a flexible magneticcomponent. Examples of flexible magnetic shielding materials includeGIRON Magnetic Shielding Film, available in a thickness of 0.85 mm fromLess EMF Inc., Latham, N.Y., USA and MagnetShield shielding film,available in a thickness of 0.3 mm from Electro Smog Shielding,Smethwick, UK. The ability of one or more sheets of the GIRON andMagnetShield films to shield against the N52 neodymium magnet was testedand the results are shown in FIG. 11 and FIG. 12. As can be seen fromthese figures, good shielding was achieved with three 40 mm×40 mm sheetsof GIRON film (2.9 mm total thickness) and with six 40 mm×40 mm sheetsof MagnetShield film (2.5 mm total thickness). A thinner material thanGIRON, MagnetShield is more flexible than GIRON and can thus be shapedmore readily than GIRON. Flexibility is a desired trait, because itallows the shield to better conform to each patient's unique face.Sheets of GIRON or MagnetShield may be cut to size, for example, usingtin shears or by forming shapes in a stamping process, among otherprocesses. If desired, sheets can be hole-punched or drilled to allowattachment of a strap. If desired, the sheets of shielding material maybe attached to one another, for example, by applying a suitableadhesive, such as a metal epoxy adhesive, between the sheets. In certainembodiments, the adhesive is applied only at the center of the sheets,leaving the edges free to allow the sheets to slide relative to oneanother during flexing. In certain embodiments, the magnet brings thesheets of shielding material together, making attachment unnecessary. Incertain embodiments, the edges of the stacked sheets may be covered by,for example, by a cloth (e.g., a cloth garter), a foam, or a flexibleframe (e.g., an injection molded frame) with a slotted perimeter intowhich the sheets can be inserted and held (e.g., analogous to theflexible frames that are used to hold and surround a ski goggle lens,for one or both eyes). It may also be desirable to attach the magnet tothe outer surface of the flexible shield, for example, using a suitableadhesive such as an epoxy adhesive, to ensure that there is no movementof the magnet relative to the shield, for example, by the patient or bymovement relative to the shield if the magnet is accidentally dropped orpushed.

In some embodiments, an optional elastic headband may used as a straparound the head, holding the eye patch in place and better conformingthe magnetic shielding material to the patient's face. This featureallows for minimal movement of the eye patch and yet can still be easilyremoved, for example, to add eye drops. This material should be elasticto allow for the eye patch to be pulled toward the face. Sports headbandmaterials may be used for this application because they are made to notbe exceptionally tight and still add the security desired for thedevice. The strap may be made adjustable in length in case the patch iseither too tight or not held tightly enough against the patients face. Aspecific example of a strap material is a silicone backed elastic suchas that available from Sew Sassy Fabrics, Huntsville, Ala., USA. Atension adjusting part like those commonly used among sunglass wearers,for example, a cord lock (e.g., a toggle spring stop single hole stringcord lock, etc.), may be used to adjust strap tension.

Although various embodiments are specifically illustrated and describedherein, it will be appreciated that modifications and variations of thepresent invention are covered by the above teachings and are within thepurview of any appended claims without departing from the spirit andintended scope of the invention.

1. A magnetic eye shield comprising a magnet that when worn by a patientis configured to generate an intraocular magnetic field of sufficientmagnitude and direction to move a magnetic therapeutic and/or diagnosticagent positioned inside the eye to a target tissue within the eye. 2.The magnetic eye shield of claim 1, wherein the magnetic eye shield isselected from an eye patches, eyeglasses and goggles.
 3. The magneticeye shield of claim 1, wherein the magnetic field generated by themagnet ranges from 0.1 Tesla to 10.0 Tesla.
 4. The magnetic eye shieldof claim 1, wherein the magnet is a rare earth magnet.
 5. The magneticeye shield of claim 1, wherein the magnet is an electromagnet comprisinga conductive coil and a source of electrical power in electricalcommunication with the conductive coil.
 6. The magnetic eye shield ofclaim 1, wherein the magnetic eye shield is configured to center themagnetic field of the magnet with the optical axis of the eye.
 7. Themagnetic eye shield of claim 1, wherein the magnetic eye shield isconfigured to generate an intraocular magnetic field that is strongestat the periphery of the cornea.
 8. The magnetic eye shield of claim 1,wherein the magnetic eye shield is configured to generate an intraocularmagnetic field that is strongest at the apex of the cornea.
 9. Themagnetic eye shield of claim 1, wherein the magnetic eye shieldcomprises a plurality of magnets.
 10. The magnetic eye shield of claim1, wherein the magnetic eye shield comprises a securement structure thatis adapted to secure the magnetic eye shield to the head of the patient.11. The magnetic eye shield of claim 10, wherein the securementstructure is selected from a strap and adhesive strip.
 12. The magneticeye shield of claim 1, wherein the magnetic therapeutic and/ordiagnostic agent is a ferromagnetic or ferrimagnetic therapeutic and/ordiagnostic agent.
 13. A kit comprising a magnetic eye shield inaccordance with claim 1 and a container of a magnetic diagnostic and/oror therapeutic agent.
 14. The kit of claim 13, further comprising aninjection device.
 15. The kit of claim 13, wherein the magnetictherapeutic and/or diagnostic agent is a ferromagnetic or ferrimagnetictherapeutic and/or diagnostic agent.
 16. The kit of claim 13, whereinthe magnetic therapeutic and/or diagnostic agent is selected from one ormore of magnetic stem cells, magnetic corneal endothelial cells,magnetic retinal pigment epithelial cells, magnetic trabecular meshworkcells, magnetic antibodies, magnetic growth factors, and magneticcytokines.
 17. The kit of claim 13, wherein the magnet is anelectromagnet comprising a conductive coil and wherein the kit furthercomprises an inductive charging unit.
 18. A method of treatmentcomprising intraocularly introducing a magnetic therapeutic and/ordiagnostic agent into an eye of a patient and fitting a magnetic eyeshield to the head of the patient, wherein the magnetic eye shield isconfigured to generate an intraocular magnetic field of sufficientmagnitude and direction to move the magnetic therapeutic and/ordiagnostic agent positioned inside the eye to a target tissue within theeye and wherein the magnetic therapeutic and/or diagnostic agent may beintroduced to the patient before or after fitting the magnetic eyeshield to the head of the patient.
 19. The method of claim 18, whereinthe magnetic therapeutic and/or diagnostic agent is injected into theanterior chamber of the eye and wherein the magnetic therapeutic and/ordiagnostic agent is directed to the apex of the cornea.
 20. The methodof claim 18, wherein the magnetic therapeutic and/or diagnostic agent isinjected into the anterior chamber of the eye and wherein the magnetictherapeutic and/or diagnostic agent is directed to the periphery of thecornea.